The mechanism of the regulatory effect of T-cell mediators on the antibody response is currently under investigation. In vitro co-cultivation and immunization procedures have been used to examine the ability of human peripheral leucocytes (HPL) to reconstitute the antibody response of a population of T-cell deficient mouse lymphocytes to the antigen sheep erythrocytes. Regression analysis of HPL dose response experiments suggest that the HPL contribute a single reconstituting cellular function to the T-cell depleted mouse lymphocytes. The "helper cells" in the HPL population have been shown to be non-phagocytic, radio-resistant, and capable of mediating the facilitative effect via a soluble factor. The soluble mediator has been shown to be released by the HPL when the cells are stimulated by either allogeneic lymphocytes or T-cell mitogens. The results therefore suggest that appropriately stimulated human lymphocytes are capable of replacing one of the t-helper cell deficiencies in the mouse lymphocyte population. It has been shown, however, that the HPL-derived lymphokine does not totally replace the requirement for syngeneic mouse T-cells. If the residual T-cells (approximately 3%) in the mouse lymphocyte population are killed by anti-T serum and complement, the antibody response of the remaining B-cells in the presence of the HPL-derived lymphokine is reduced by 90%.